Circulatory Shock: Critical Care Review

The
n e w e ng l a n d j o u r na l
of
m e dic i n e
review article
critical care medicine
Simon R. Finfer, M.D., and Jean-Louis Vincent, M.D., Ph.D., Editors
Circulatory Shock
Jean-Louis Vincent, M.D., Ph.D., and Daniel De Backer, M.D., Ph.D.
From the Department of Intensive Care,
Erasme Hospital, Université Libre de Bruxelles, Brussels. Address reprint requests to
Dr. Vincent at the Department of Intensive
Care, Erasme University Hospital, Rte. de
Lennik 808, B-1070 Brussels, Belgium, or
at [email protected].
N Engl J Med 2013;369:1726-34.
DOI: 10.1056/NEJMra1208943
Copyright © 2013 Massachusetts Medical Society.
S
hock is the clinical expression of circulatory failure that
­results in inadequate cellular oxygen utilization. Shock is a common condition in critical care, affecting about one third of patients in the intensive care
unit (ICU).1 A diagnosis of shock is based on clinical, hemodynamic, and biochemical signs, which can broadly be summarized into three components. First,
systemic arterial hypotension is usually present, but the magnitude of the hypotension may be only moderate, especially in patients with chronic hypertension. Typically, in adults, the systolic arterial pressure is less than 90 mm Hg or the mean
arterial pressure is less than 70 mm Hg, with associated tachycardia. Second, there
are clinical signs of tissue hypoperfusion, which are apparent through the three
“windows” of the body2: cutaneous (skin that is cold and clammy, with vasoconstriction and cyanosis, findings that are most evident in low-flow states), renal
(urine output of <0.5 ml per kilogram of body weight per hour), and neurologic
(altered mental state, which typically includes obtundation, disorientation, and
confusion). Third, hyperlactatemia is typically present, indicating abnormal cellular
oxygen metabolism. The normal blood lactate level is approximately 1 mmol per liter,
but the level is increased (>1.5 mmol per liter) in acute circulatory failure.
Pathoph ysiol o gic a l Mech a nisms
An interactive
graphic showing
initial assessment of
shock is available
at NEJM.org
Shock results from four potential, and not necessarily exclusive, pathophysiological
mechanisms3: hypovolemia (from internal or external fluid loss), cardiogenic factors (e.g., acute myocardial infarction, end-stage cardiomyopathy, advanced valvular
heart disease, myocarditis, or cardiac arrhythmias), obstruction (e.g., pulmonary
embolism, cardiac tamponade, or tension pneumothorax), or distributive factors
(e.g., severe sepsis or anaphylaxis from the release of inflammatory mediators)
(Fig. 1A and the interactive graphic, available at NEJM.org). The first three mechanisms are characterized by low cardiac output and, hence, inadequate oxygen transport. In distributive shock, the main deficit lies in the periphery, with decreased
systemic vascular resistance and altered oxygen extraction. Typically, in such cases
cardiac output is high, although it may be low as a result of associated myocardial
depression. Patients with acute circulatory failure often have a combination of these
mechanisms. For example, a patient with distributive shock from severe pancreatitis,
anaphylaxis, or sepsis may also have hypovolemia and cardiogenic shock from
myocardial depression.
Differ en t i a l Di agnosis
Septic shock, a form of distributive shock, is the most common form of shock
among patients in the ICU, followed by cardiogenic and hypovolemic shock;
­obstructive shock is relatively rare (Fig. 1B and 1C). In a trial involving more than
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Critical Care Medicine
1600 patients with shock who were randomly assigned to receive either dopamine or norepinephrine, septic shock occurred in 62% of the patients,
cardiogenic shock in 16%, hypovolemic shock in
16%, other types of distributive shock in 4%, and
obstructive shock in 2%.4
The type and cause of shock may be obvious
from the medical history, physical examination,
or clinical investigations. For example, shock
after traumatic injury is likely to be hypovolemic
(due to blood loss), but cardiogenic shock or
distributive shock may also occur, alone or in
combination, caused by such conditions as cardiac tamponade or spinal cord injury. A full clinical examination should include assessment of
skin color and temperature, jugular venous distention, and peripheral edema. The diagnosis
can be refined with point-of-care echocardiographic evaluation, which includes assessment
for pericardial effusion, measurement of left and
right ventricular size and function, assessment for
respiratory variations in vena cava dimensions,
and calculation of the aortic velocity–time integral, a measure of stroke volume. Whenever possible, focused echocardiography should be performed as soon as possible in any patient
presenting with shock (Fig. 1A).5,6
Ini t i a l A pproach
t o the Pat ien t in Sho ck
Ventilatory Support
The administration of oxygen should be started immediately to increase oxygen delivery and prevent
pulmonary hypertension. Pulse oximetry is often
unreliable as a result of peripheral vasoconstriction, and precise determination of oxygen requirements will often require blood gas monitoring.
Mechanical ventilation by means of a mask
rather than endotracheal intubation has a limited place in the treatment of shock because
technical failure can rapidly result in respiratory
and cardiac arrest. Hence, endotracheal intubation should be performed to provide invasive
mechanical ventilation in nearly all patients with
severe dyspnea, hypoxemia, or persistent or worsening acidemia (pH, <7.30). Invasive mechanical
ventilation has the additional benefits of reducing the oxygen demand of respiratory muscles
and decreasing left ventricular afterload by increasing intrathoracic pressure. An abrupt decrease in arterial pressure after the initiation of
invasive mechanical ventilation strongly suggests
hypovolemia and a decrease in venous return.
The use of sedative agents should be kept to a
minimum to avoid further decreases in arterial
pressure and cardiac output.
Fluid Resuscitation
Early, adequate hemodynamic support of patients
in shock is crucial to prevent worsening organ
dysfunction and failure. Resuscitation should be
started even while investigation of the cause is
ongoing. Once identified, the cause must be corrected rapidly (e.g., control of bleeding, percutaneous coronary intervention for coronary syndromes, thrombolysis or embolectomy for massive
pulmonary embolism, and administration of antibiotics and source control for septic shock).
Unless the condition is rapidly reversed, an
arterial catheter should be inserted for monitoring of arterial blood pressure and blood sampling, plus a central venous catheter for the infusion of fluids and vasoactive agents and to guide
fluid therapy. The initial management of shock
is problem-oriented, and the goals are therefore
the same, regardless of the cause, although the
exact treatments that are used to reach those
goals may differ. A useful mnemonic to describe
the important components of resuscitation is the
VIP rule7: ventilate (oxygen administration), inn engl j med 369;18
fuse (fluid resuscitation), and pump (administration of vasoactive agents).
Fluid therapy to improve microvascular blood
flow and increase cardiac output is an essential
part of the treatment of any form of shock. Even
patients with cardiogenic shock may benefit
from fluids, since acute edema can result in a
decrease in the effective intravascular volume.
However, fluid administration should be closely
monitored, since too much fluid carries the risk
of edema with its unwanted consequences.
Pragmatic end points for fluid resuscitation
are difficult to define. In general, the objective is
for cardiac output to become preload-independent (i.e., on the plateau portion of the Frank–
Starling curve), but this is difficult to assess
clinically. In patients receiving mechanical ventilation, signs of fluid responsiveness may be identified either directly from beat-by-beat stroke-volume
measurements with the use of cardiac-output
monitors or indirectly from observed variations
in pulse pressure on the arterial-pressure tracing
during the ventilator cycle. However, such bedside
inferences have some limitations8 — notably,
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1727
The
A
n e w e ng l a n d j o u r na l
of
m e dic i n e
B Types of shock
Arterial hypotension
62%
Distributive (septic)
Signs of tissue hypoperfusion
Absent
Present
Brain
Altered mental
state
Chronic
hypotension?
Syncope
(if transient)
Circulatory
shock
Tachycardia
Mottled,
clammy
Normal
or high
2%
Obstructive
16%
16%
Cardiogenic Hypovolemic
Estimate cardiac
output or SvO2
Elevated
blood
lactate
Skin
4%
Distributive
(nonseptic)
Low
Kidney
CVP
Oliguria
Low
High
Normal cardiac
chambers and (usually)
preserved contractility
Small cardiac
chambers and normal
or high contractility
Large ventricles and
poor contractility
In tamponade: pericardial
effusion, small right and
left ventricles, dilated
inferior vena cava; in
pulmonary embolism or
pneumothorax: dilated right
ventricle, small left ventricle
Distributive shock
Hypovolemic shock
Cardiogenic shock
Obstructive shock
Distributive shock
Hypovolemic shock
Cardiogenic shock
Obstructive shock
Echocardiography
C
Vasodilatation
Loss of
plasma or
blood
volume
Obstruction
Ventricular
failure
Pericardial
tamponade
Figure 1. Initial Assessment of Shock States.
COLOR FIGURE
Shown is an algorithm for the initial assessment of a patient in shock (Panel A), relative frequencies of the main types of shock (Panel B),
Draft 9presentation
10/10/13
and schematic representations of the four main types of shock (Panel C). The algorithm starts with the most common
Author Vincent
(i.e., arterial hypotension), but hypotension is sometimes minimal or absent. CVP denotes central venous pressure,
and
SvO2 mixed
1
Fig #
venous oxygen saturation.
Title
ME
Drazen
Knoper
DE
Artist
AUTHOR PLEASE NOTE:
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Critical Care Medicine
a vasopressor temporarily while fluid resuscitation is ongoing, with the aim of discontinuing it,
if possible, after hypovolemia has been corrected.
Adrenergic agonists are the first-line vasopressors because of their rapid onset of action,
high potency, and short half-life, which allows
easy dose adjustment. Stimulation of each type
of adrenergic receptor has potentially beneficial
and harmful effects. For example, β-adrenergic
stimulation can increase blood flow but also increases the risk of myocardial ischemia as a result
of increased heart rate and contractility. Hence, the
use of isoproterenol, a pure β-adrenergic agent, is
limited to the treatment of patients with severe
bradycardia. At the other extreme, α-adrenergic
stimulation will increase vascular tone and blood
pressure but can also decrease cardiac output
and impair tissue blood flow, especially in the
hepatosplanchnic region. For this reason, phenyl­
ephrine, an almost pure α-adrenergic agent, is
rarely indicated.
We consider norepinephrine to be the vasopressor of first choice; it has predominantly
α-adren­ergic properties, but its modest β-adrener­
gic effects help to maintain cardiac output.
Administration generally results in a clinically
significant increase in mean arterial pressure,
with little change in heart rate or cardiac output.
The usual dose is 0.1 to 2.0 µg per kilogram of
body weight per minute.
Dopamine has predominantly β-adrenergic
effects at lower doses and α-adrenergic effects at
higher doses, but its effects are relatively weak.
Dopaminergic effects at very low doses (<3 µg per
kilogram per minute, given intravenously) may
selectively dilate the hepatosplanchnic and renal
circulations, but controlled trials have not shown
a protective effect on renal function,14 and its
routine use for this purpose is no longer recommended. Dopaminergic stimulation may also
have undesired endocrine effects on the hypothalamic–pituitary system, resulting in immuno­
suppression, primarily through a reduction in
the release of prolactin.
In a recent randomized, controlled, doubleblind trial, dopamine had no advantage over nor­
Vasoactive Agents
epinephrine as the first-line vasopressor agent;
Vasopressors
moreover, it induced more arrhythmias and was
If hypotension is severe or if it persists despite associated with an increased 28-day rate of
fluid administration, the use of vasopressors is death among patients with cardiogenic shock.4
indicated. It is acceptable practice to administer Administration of dopamine, as compared with
that the patient must receive ventilation with
relatively large tidal volumes, have no spontaneous breathing effort (which usually requires the
administration of sedatives or even muscle relaxants), and be free of major arrhythmia and right
ventricular dysfunction. A passive leg-raising test
is an alternative method9 but requires a rapidresponse device, since the effect is transient.
Regardless of the test used, there remains a gray
zone in which it is difficult to predict a patient’s
response to intravenous fluids.
A fluid-challenge technique should be used to
determine a patient’s actual response to fluids,
while limiting the risks of adverse effects. A fluid
challenge incorporates four elements that should
be defined in advance.10 First, the type of fluid
must be selected. Crystalloid solutions are the
first choice, because they are well tolerated and
cheap. The use of albumin to correct severe hypoalbuminemia may be reasonable in some patients.11 (A detailed examination of the choice of
resuscitation fluids was provided in a previous
article in this series12 and thus is not included in
this review.) Second, the rate of fluid administration must be defined. Fluids should be infused rapidly to induce a quick response but not
so fast that an artificial stress response develops;
typically, an infusion of 300 to 500 ml of fluid
is administered during a period of 20 to 30 minutes.13 Third, the objective of the fluid challenge
must be defined. In shock, the objective is usually an increase in systemic arterial pressure,
although it could also be a decrease in heart rate
or an increase in urine output. Finally, the safety
limits must be defined. Pulmonary edema is the
most serious complication of fluid infusion. Although it is not a perfect guideline, a limit in
central venous pressure of a few millimeters of
mercury above the baseline value is usually set to
prevent fluid overload.13
Stimulation of the patient and any other
change in therapy should be avoided during the
test. Fluid challenges can be repeated as required
but must be stopped rapidly in case of non­
response in order to avoid fluid overload.
n engl j med 369;18
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1729
The
n e w e ng l a n d j o u r na l
norepinephrine, may also be associated with
higher rates of death among patients with septic
shock.15 Hence, we no longer recommend dopamine for the treatment of patients with shock.
Epinephrine, which is a stronger agent, has
predominantly β-adrenergic effects at low doses,
with α-adrenergic effects becoming more clinically significant at higher doses. However, epinephrine administration can be associated with
an increased rate of arrhythmia16,17 and a decrease
in splanchnic blood flow16 and can increase blood
lactate levels, probably by increasing cellular metabolism.16,18 Prospective, randomized studies have
not shown any beneficial effects of epinephrine
over norepinephrine in septic shock.17,18 We reserve epinephrine as a second-line agent for severe cases.13
The use of other strong vasopressor agents as
continuous infusions (e.g., angiotensin or metaraminol) has largely been abandoned. Nonselective inhibition of nitric oxide has not been shown
to be beneficial in patients with cardiogenic
shock19 and is detrimental in patients with septic shock.20
Vasopressin deficiency can develop in patients with very hyperkinetic forms of distributive shock, and the administration of low-dose
vasopressin may result in substantial increases
in arterial pressure. In the Vasopressin and Septic Shock Trial (VASST), investigators found that
the addition of low-dose vasopressin to norepinephrine in the treatment of patients with septic
shock was safe21 and may have been associated
with a survival benefit for patients with forms of
shock that were not severe and for those who
also received glucocorticoids.22 Vasopressin should
not be used at doses higher than 0.04 U per minute and should be administered only in patients
with a high level of cardiac output.
Terlipressin, an analogue of vasopressin, has
a duration of action of several hours, as compared with minutes for vasopressin. For this
reason, we do not believe it offers an advantage
over vasopressin in the ICU. Vasopressin derivatives with more selective V1-receptor activity are
currently being studied.
Inotropic Agents
We consider dobutamine to be the inotropic
agent of choice for increasing cardiac output, regardless of whether norepinephrine is also being
given. With predominantly β-adrenergic proper1730
n engl j med 369;18
of
m e dic i n e
ties, dobutamine is less likely to induce tachycardia than isoproterenol. An initial dose of just a
few micrograms per kilogram per minute may
substantially increase cardiac output. Intravenous
doses in excess of 20 µg per kilogram per minute
usually provide little additional benefit. Dobutamine has limited effects on arterial pressure, although pressure may increase slightly in patients
with myocardial dysfunction as the primary abnormality or may decrease slightly in patients
with underlying hypovolemia. Instead of routine
administration of a fixed dose of dobutamine to
increase oxygen delivery to supranormal, predetermined levels, the dose should be adjusted on
an individual basis to achieve adequate tissue
perfusion. Dobutamine may improve capillary
perfusion in patients with septic shock, independent of its systemic effects.23
Phosphodiesterase type III inhibitors, such as
milrinone and enoximone, combine inotropic and
vasodilating properties. By decreasing the metabolism of cyclic AMP, these agents may reinforce the effects of dobutamine. They may also
be useful when β-adrenergic receptors are downregulated or in patients recently treated with
beta-blockers. However, phosphodiesterase type
III inhibitors may have unacceptable adverse effects in patients with hypotension, and the long
half-lives of these agents (4 to 6 hours) prevent
minute-to-minute adjustment. Hence, intermittent, short-term infusions of small doses of
phosphodiesterase III inhibitors may be preferable to a continuous infusion in shock states.
Levosimendan, a more expensive agent, acts
primarily by binding to cardiac troponin C and
increasing the calcium sensitivity of myocytes,
but it also acts as a vasodilator by opening ATPsensitive potassium channels in vascular smooth
muscle. However, this agent has a half-life of
several days, which limits the practicality of its
use in acute shock states.
Vasodilators
By reducing ventricular afterload, vasodilating
agents may increase cardiac output without increasing myocardial demand for oxygen. The
major limitation of these drugs is the risk of decreasing arterial pressure to a level that compromises tissue perfusion. Nevertheless, in some
patients, prudent use of nitrates and possibly
other vasodilators may improve microvascular
perfusion and cellular function.24
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Critical Care Medicine
Mech a nic a l Supp or t
A
Mechanical support with intraaortic balloon
counterpulsation (IABC) can reduce left ventricular afterload and increase coronary blood flow.
However, a recent randomized, controlled trial
showed no beneficial effect of IABC in patients
with cardiogenic shock,25 and its routine use in
cardiogenic shock is not currently recommended.
Venoarterial extracorporeal membrane oxygenation
(ECMO) may be used as a temporary lifesaving
measure in patients with reversible cardiogenic
shock or as a bridge to heart transplantation.26
G oa l s of Hemody na mic Supp or t
B
Arterial Pressure
The primary goal of resuscitation should be not
only to restore blood pressure but also to provide
adequate cellular metabolism, for which the correction of arterial hypotension is a prerequisite.
Restoring a mean systemic arterial pressure of
65 to 70 mm Hg is a good initial goal, but the
level should be adjusted to restore tissue perfusion, assessed on the basis of mental status, skin
appearance, and urine output, as described above.
In patients with oliguria, in particular, the effects
of a further increase in arterial pressure on urine
output should be assessed regularly, unless acute
renal failure is already established. Conversely, a
mean arterial pressure lower than 65 to 70 mm Hg
may be acceptable in a patient with acute bleeding
who has no major neurologic problems, with the
aim of limiting blood loss and associated coagulopathy, until the bleeding is controlled.
Cardiac Output and Oxygen Delivery
Since circulatory shock represents an imbalance
between oxygen supply and oxygen requirements,
maintaining adequate oxygen delivery to the tissues is essential, but all the strategies to achieve
this goal have limitations. After correction of hypoxemia and severe anemia, cardiac output is the
principal determinant of oxygen delivery, but the
optimal cardiac output is difficult to define. Cardiac output can be measured by means of various
techniques, each of which has its own benefits
and drawbacks.6 Absolute measures of cardiac
output are less important than monitoring trends
in response to interventions such as a fluid challenge. The targeting of a predefined cardiac output is not advisable, since the cardiac output that
n engl j med 369;18
Figure 2. Sidestream Dark-Field Images of Sublingual
Microcirculation in a Healthy Volunteer and a Patient
with Septic Shock.
The microcirculation in the healthy volunteer is characterized by dense capillaries that are consistently perfused
(Panel A, arrows), whereas in the patient with septic
shock, the density of the capillaries is diminished, and
many of the capillaries have stopped or intermittent
flow (Panel B, arrows).
is needed will vary among patients and in the
same patient over time.
Measurements of mixed venous oxygen saturation (SvO2) may be helpful in assessing the
adequacy of the balance between oxygen demand and supply; SvO2 measurements are also
very useful in the interpretation of cardiac output.27 SvO2 is typically decreased in patients with
low-flow states or anemia but is normal or high
in those with distributive shock. Its surrogate,
central venous oxygen saturation (ScvO2), which
is measured in the superior vena cava by means
of a central venous catheter, reflects the oxygen
saturation of the venous blood from the upper
half of the body only. Under normal circumstances,
ScvO2 is slightly less than SvO2, but in critically
ill patients it is often greater. Rivers et al.28 found
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1731
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Phase Focus
Microcirculatory Variables
Salvage
Optimization
Stabilization
De-escalation
Obtain a
minimal
acceptable
blood pressure
Provide
adequate
oxygen
availability
Provide organ
support
Wean from
vasoactive
agents
Perform
lifesaving
measures
Optimize
cardiac output,
SvO2, lactate
Minimize
complications
Achieve a
negative
fluid balance
Figure 3. Four Phases in the Treatment of Shock.
COLOR FIGURE
The salvage phase focuses on achieving a blood pressure and cardiac outDraft 6
10/15/13
put compatible with immediate survival and performing
lifesaving proceAuthor Vincent
dures to treat the underlying cause of shock. The Fig
optimization
phase focus3
#
Title
es on promoting cellular oxygen availability and monitoring
cardiac output,
mixed venous oxygen saturation (SvO2), and lactate
levels. The stabilization
ME
phase focuses on preventing organ dysfunction, even
after
hemodynamic
DE
Drazen
Artist focuses
Knoper on weaning
stability has been achieved. The de-escalation phase
AUTHOR PLEASE
NOTE:
the patient from vasoactive agents and providing treatments
to help
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Please check carefully
achieve a negative fluid balance.
Issue date 10/31/13
that in patients presenting to the emergency
department with septic shock, a treatment algorithm targeting an ScvO2 of at least 70% during
the first 6 hours was associated with decreased
rates of death. The robustness of this finding is
currently being evaluated in three multicenter
trials. (ClinicalTrials.gov numbers, NCT00975793
and NCT00510835; and Current Controlled Trials
number, ISRCTN36307479).
The development of handheld devices for orthogonal polarization spectral (OPS) imaging and its
successor, sidestream dark-field (SDF) imaging,
is providing new means of directly visualizing
the microcirculation and evaluating the effects of
interventions on microcirculatory flow in easily
accessible surfaces, such as the sublingual area.30
Microcirculatory changes, including decreased
capillary density, a reduced proportion of perfused
capillaries, and increased heterogeneity of blood
flow, have been identified in various types of circulatory shock (Fig. 2), and the persistence of these
alterations is associated with worse outcomes.31
Near-infrared spectroscopy is a technique that
uses near-infrared light to determine tissue oxygen saturation from the fractions of oxyhemoglobin and deoxyhemoglobin. Analysis of the
changes in tissue oxygen saturation during a
brief episode of forearm ischemia can be used to
quantify microvascular dysfunction32; such alterations are associated with worse outcomes.33 Various therapeutic interventions have been shown
to have an effect on these microcirculatory variables, but whether therapy that is guided by
monitoring or targeting the microcirculation
can improve outcomes requires further study
and cannot be recommended at this time.
Ther a peu t ic Pr ior i t ie s
a nd G oa l s
Blood Lactate Level
An increase in the blood lactate level reflects abnormal cellular function. In low-flow states, the
primary mechanism of hyperlactatemia is tissue
hypoxia with development of anaerobic metabolism, but in distributive shock, the pathophysiology is more complex and may also involve increased
glycolysis and inhibition of pyruvate dehydrogenase. In all cases, alterations in clearance can be
due to impaired liver function.
The value of serial lactate measurements in
the management of shock has been recognized
for 30 years.29 Although changes in lactate take
place more slowly than changes in systemic arterial pressure or cardiac output, the blood lactate
level should decrease over a period of hours with
effective therapy. In patients with shock and a
blood lactate level of more than 3 mmol per liter,
Jansen et al.24 found that targeting a decrease
of at least 20% in the blood lactate level over a
2-hour period seemed to be associated with reduced in-hospital mortality.
1732
n engl j med 369;18
There are essentially four phases in the treatment
of shock, and therapeutic goals and monitoring
need to be adapted to each phase (Fig. 3). In the
first (salvage) phase, the goal of therapy is to
achieve a minimum blood pressure and cardiac
output compatible with immediate survival. Minimal monitoring is needed; in most cases, invasive
monitoring can be restricted to arterial and central venous catheters. Lifesaving procedures (e.g.,
surgery for trauma, pericardial drainage, revascularization for acute myocardial infarction, and antibiotics for sepsis) are needed to treat the underlying cause. In the second (optimization) phase, the
goal is to increase cellular oxygen availability, and
there is a narrow window of opportunity for interventions targeting hemodynamic status.28 Adequate hemodynamic resuscitation reduces inflammation, mitochondrial dysfunction, and caspase
activation.34,35 Measurements of SvO2 and lactate
levels may help guide therapy, and monitoring of
cardiac output should be considered. In the third
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Critical Care Medicine
(stabilization) phase, the goal is to prevent organ
dysfunction, even after hemodynamic stability has
been achieved. Oxygen supply to the tissues is no
longer the key problem, and organ support becomes more relevant. Finally, in the fourth (deescalation) phase, the goal is to wean the patient
from vasoactive agents and promote spontaneous
polyuria or provoke fluid elimination through the
use of diuretics or ultrafiltration to achieve a negative fluid balance.
C onclusions
Circulatory shock is associated with high morbidity and mortality. Prompt identification is es-
sential so that aggressive management can be
started. Appropriate treatment is based on a good
understanding of the underlying pathophysiological mechanisms. Treatment should include correction of the cause of shock and hemodynamic
stabilization, primarily through fluid infusion
and administration of vasoactive agents. The patient’s response can be monitored by means of
careful clinical evaluation and blood lactate measurements; microvascular evaluation may be feasible in the future.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
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